AMPK alpha 1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration

Summary, in English

Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPK alpha 1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPK alpha 1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPK alpha 1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPK alpha 1 was required for muscle regeneration. Cell-based experiments revealed that AMPK alpha 1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPK alpha 1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPK alpha 1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKK beta. In conclusion, AMPK alpha 1 is crucial for phagocytosis-induced macrophage skewing from a pro-to anti-inflammatory phenotype at the time of resolution of inflammation.

• Författare: Remi Mounier; Marine Theret; Ludovic Arnold; Sylvain Cuvellier; Laurent Bultot; Olga Göransson; Nieves Sanz; Arnaud Ferry; Kei Sakamoto; Marc Foretz; Benoit Viollet; Benedicte Chazaud
• Avdelning/ar: Proteinfosforylering; EXODIAB: Excellence of Diabetes Research in Sweden
• Publiceringsår: 2013
• Språk: Engelska
• Sidor: 251-264
• Publikation/Tidskrift/Serie: Cell Metabolism
• Volym: 18
• Issue: 2
• Länkar: http://dx.doi.org/10.1016/j.cmet.2013.06.017
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Cell and Molecular Biology
• Status: Published
• Forskningsgrupp: Protein Phosphorylation
• ISBN/ISSN/Övrigt: ISSN: 1550-4131